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Crystal structure of a heparin‐ and integrin‐binding segment of human fibronectin
Author(s) -
Sharma Amit,
Askari Janet A.,
Humphries Martin J.,
Jones E.Yvonne,
Stuart David I.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.6.1468
Subject(s) - fibronectin , biology , integrin , binding site , plasma protein binding , microbiology and biotechnology , peptide sequence , biochemistry , gene , receptor , extracellular matrix
The crystal structure of human fibronectin (FN) type III repeats 12–14 reveals the primary heparin‐binding site, a clump of positively charged residues in FN13, and a putative minor site ∼60 Å away in FN14. The IDAPS motif implicated in integrin α 4 β 1 binding is at the FN13–14 junction, rendering the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for α 4 β 1 binding to FN12–14. The PRARI motif may represent a new class of integrin‐binding sites. The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.